TGI Friday! Our weekly round-up of recently published ME/CFS research abstracts | 8 August 2013

August 9, 2013

From the Journal of Medical Virology, 25 July 2013.

Persistent human herpesvirus-6 infection in patients with an inherited form of the virus

Shara N. Pantry(1), Maria M. Medveczky(1), Jesse H. Arbuckle(1), Janos Luka(2), Jose G. Montoya(3), Jianhong Hu(4), Rolf Renne(4), Daniel Peterson(5), Joshua C. Pritchett(6), Dharam V. Ablashi(6), Peter G. Medveczky(1,*)
1) Department of Molecular Medicine, University of South Florida, Morsani College of Medicine, Tampa, Florida
2) Bioworld Consulting Laboratories, Mt. Airy, Maryland
3) Department of Infectious Disease, Stanford University, Stanford, California
4) Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida
5) Sierra Internal Medicine, Incline Village, Nevada
6) The HHV-6 Foundation, Santa Barbara, California
* Correspondence to: Peter G. Medveczky, University of South Florida College of Medicine, 12901 Bruce B. Blvd., MDC Box 7, Tampa, FL 33612. E-mail:


Human herpesvirus-6 (HHV-6)A and 6B are ubiquitous betaherpesviruses viruses with lymphotropic and neurotropic potential. As reported earlier, these viruses establish latency by integration into the telomeres of host chromosomes.

Chromosomally integrated HHV-6 (CIHHV-6) can be transmitted vertically from parent to child. Some CIHHV-6 patients are suffering from neurological symptoms, while others remain asymptomatic.

Four patients with CIHHV-6 and CNS dysfunction were treated with valganciclovir or foscarnet. HHV-6 replication was detected by reverse transcriptase polymerase chain reaction amplification of a late envelope glycoprotein.

In this study we also compared the inherited and persistent HHV-6 viruses by DNA sequencing. The prevalence of CIHHV-6 in this cohort of adult patients from the USA suffering from a wide range of neurological symptoms including long-term fatigue were found significantly greater than the reported 0.8% in the general population.

Long-term antiviral therapy inhibited HHV-6 replication as documented by loss of viral mRNA production. Sequence comparison of the mRNA and the inherited viral genome revealed that the transcript is produced by an exogenous virus.

In conclusion, the data presented here document that some individuals with CIHHV-6 are infected persistently with exogenous HHV-6 strains that lead to a wide range of neurological symptoms; the proposed name for this condition is inherited herpesvirus 6 syndrome or IHS. J. Med. Virol. © 2013 Wiley Periodicals, Inc.

From Evidence Based Complementary and Alternative Medicine, 4 June 2013. E-published first.

Efficacy and safety of medicinal plants or related natural products for fibromyalgia: a systematic review.

de Souza Nascimento S, Desantana JM, Nampo FK, Ribeiro EA, da Silva DL, Araújo-Júnior JX, da Silva Almeida JR, Bonjardim LR, de Souza Araújo AA, Quintans-Júnior LJ.
Department of Physiology, Federal University of Sergipe, Marechal Rondom Avenue, 49000-100 São Cristovão, SE, Brazil.


To assess the effects of medicinal plants (MPs) or related natural products (RNPs) on fibromyalgia (FM) patients, we evaluate the possible benefits and advantages of MP or RNP for the treatment of FM based on eight randomized placebo-controlled trials (RCTs) involving 475 patients.

The methodological quality of all studies included was determined according to JADAD and “Risk of Bias” with the criteria in the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0.

Evidence suggests significant benefits of MP or RNP in sleep disruption, pain, depression, joint stiffness, anxiety, physical function, and quality of life.

Our results demonstrated that MP or RNP had significant effects on improving the symptoms of FM compared to conventional drug or placebo; longer tests are required to determine the duration of the treatment and characterize the long-term safety of using MP, thus suggesting effective alternative therapies in the treatment of pain with minimized side effects.

From the Journal of Psychosomatic Research, 22 July 2013 (E-published first).

The process of cognitive behaviour therapy for chronic fatigue syndrome: Which changes in perpetuating cognitions and behaviour are related to a reduction in fatigue?

Marianne J. Heins*, Hans Knoop, William J. Burk, Gijs Bleijenberg
* Corresponding author at: Radboud University Nijmegen Medical Centre, Expert Centre for Chronic Fatigue, 4628, PO Box 9101, 6500 HB Nijmegen, The Netherlands.



Cognitive behaviour therapy (CBT) can significantly reduce fatigue in chronic fatigue syndrome (CFS), but little is known about the process of change taking place during CBT. Based on a recent treatment model (Wiborg et al. J Psych Res 2012), we examined how (changes in) cognitions and behaviour are related to the decrease in fatigue.


We included 183 patients meeting the US Centers for Disease Control criteria for CFS, aged 18 to 65years, starting CBT. We measured fatigue and possible process variables before treatment; after 6, 12 and 18weeks; and after treatment. Possible process variables were sense of control over fatigue, focusing on symptoms, self-reported physical functioning, perceived physical activity and objective (actigraphic) physical activity. We built multiple regression models, explaining levels of fatigue during therapy by (changes in) proposed process variables.


We observed large individual variation in the patterns of change in fatigue and process variables during CBT for CFS. Increases in the sense of control over fatigue, perceived activity and self-reported physical functioning, and decreases in focusing on symptoms explained 20 to 46% of the variance in fatigue. An increase in objective activity was not a process variable.


A change in cognitive factors seems to be related to the decrease in fatigue during CBT for CFS. The pattern of change varies considerably between patients, but changes in process variables and fatigue occur mostly in the same period.

From Frontiers in Physiology, 24 July 2013.

Migraine in gulf war illness and chronic fatigue syndrome: prevalence, potential mechanisms, and evaluation.

Rayhan RU, Ravindran MK, Baraniuk JN.
Division of Rheumatology, Immunology and Allergy, Department of Medicine, Georgetown University Washington, DC, USA.



To assess the prevalence of headache subtypes in Gulf War Illness (GWI) and Chronic Fatigue Syndrome (CFS) compared to controls.


Approximately, 25% of the military personnel who served in the 1990-1991 Persian Gulf War have developed GWI. Symptoms of GWI and CFS have considerable overlap, including headache complaints. Migraines are reported in CFS. The type and prevalence of headaches in GWI have not been adequately assessed.


50 GWI, 39 CFS and 45 controls had structured headache evaluations based on the 2004 International Headache Society criteria.
All subjects had history and physical examinations, fatigue and symptom related questionnaires, measurements of systemic hyperalgesia (dolorimetry), and assessments for exclusionary conditions.


Migraines were detected in 64% of GWI (odds ratio = 11.6 [4.1-32.5]) (mean [±95% CI]) and 82% of CFS subjects (odds ratio = 22.5 [7.8-64.8]) compared to only 13% of controls. There was a predominance of females in the CFS compared to GWI and controls. However, migraine status was independent of gender in GWI and CFS groups (x (2) = 2.7; P = 0.101). Measures of fatigue, pain, and other ancillary criteria were comparable between GWI and CFS subjects with and without headache.


The high prevalence of migraine in CFS was confirmed and extended to GWI subjects. GWI and CFS may share dysfunctional central pathophysiological pathways that contribute to migraine and subjective symptoms. The high migraine prevalence warrants the inclusion of a structured headache evaluation in GWI and CFS subjects, and treatment when present.

From BMC Research Notes, 2 August 2013.

A pilot registry of unexplained fatiguing illnesses and chronic fatigue syndrome

Dana J Brimmer(1,3,*), Elizabeth Maloney(1,5), Rebecca Devlin(2), James F Jones(1), Roumiana Boneva(1), Caryn Nagler(4), Lisa LeRoy(4), Scott Royal(4), Hao Tian (1), Jin-Mann S Lin (1), Jennifer Kasten (4,6)

1) Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road, MS-G41, Atlanta, GA 30033, USA
2) Abt SRBI, 640 North LaSalle, Suite 640, Chicago, IL 60610, USA
3) McKing Consulting, 2900 Chamblee Tucker Road, Building 10, Suite 100, Atlanta, GA 30341, USA
4) Abt Associates, 55 Wheeler Street, Cambridge, MA 02138-1168, USA
5) Current Affiliation: Food and Drug Administration, Office of Surveillance and Epidemiology, 10903 New Hampshire Ave., Building 22, Rm 2476, Mail Stop 3411, Silver Spring, MD 20993, USA
6) Current Affiliation: JBS International, Inc., 5515 Security Lane, Suite 800, North Bethesda, MA 20852, USA
*) Corresponding author. Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road, MS-G41, Atlanta, GA 30033, USA

Abstract (provisional)


Chronic fatigue syndrome (CFS) has no diagnostic clinical signs or biomarkers, so diagnosis requires ruling out conditions with similar signs and symptoms.

We conducted a pilot registry of unexplained fatiguing illnesses and CFS to determine the feasibility of establishing and operating a registry and implementing an education outreach initiative. The pilot registry was conducted in Bibb County, Georgia.

Patient referrals were obtained from healthcare providers who were identified by using various education outreach initiatives. These referrals were later supplemented with self-referrals by members of a local CFS support group. All patients meeting referral criteria were invited to participate in a screening interview to determine eligibility.

If patients met registry criteria, they were invited to a one-day clinic for physical and laboratory evaluations. We classified patients based on the 1994 case definition.


We registered 827 healthcare providers. Forty-two providers referred 88 patients, and 58 patients (66%) completed clinical evaluation. Of the 188 CFS support group members, 53 were self-referred and 46 (87%) completed the clinical evaluation. Of the 104 participants completing evaluation, 36% (n = 37) met the criteria for CFS, 17% (n = 18) had insufficient fatigue or symptoms (ISF), and 47% (n = 49) were found to have exclusionary medical or psychiatric illnesses.

Classification varied significantly by type of referral but not by previous history of CFS diagnosis. Healthcare providers referred more patients who were classified as CFS as compared to support group referrals in which more exclusionary conditions were identified. Family practice and internal medicine specialties made the most referrals and had the highest number of CFS cases. We conducted three CME events, held three “Meet and Greet” sessions, visited four large clinical health practices and health departments, mailed five registry newsletters, and conducted in-person office visits as part of education outreach, which contributed to patient referrals.


Referrals from healthcare providers and self-referrals from the patient support group were important to registry enrollment. The number of potentially treatable conditions that were identified highlights the need for continued medical management in this population, as well as the limitations of registries formed without clinical examination. Education initiatives were successful in part because of partnerships with local organizations.

From ‘Anaerobe'. August 2913 (open access article)

Clinical microbiology

High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients

Marc Frémont(a), Danny Coomans(b), Sebastien Massart©, Kenny De Meirleir(d)
(a) R.E.D Laboratories NV, Z-1 Researchpark 100, 1731 Zellik, Belgium
(b) Biostatistics and Medical Informatics Department, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
(c) DNAVision SA, Av. Georges Lemaitre 25, 6041 Gosselies, Belgium
(d) Department of Human Physiology, Vrije Universiteit Brussel, Pleinlaan 2, 1051 Brussels, Belgium


• We looked for alterations of gut microbiota in chronic fatigue syndrome patients.
• Patients and controls from two geographical origins were included in the study.
• Gut flora composition differed between people from different geographical origins.
• Significant alterations of gut microbiota composition were observed in patients.


Human intestinal microbiota plays an important role in the maintenance of host health by providing energy, nutrients, and immunological protection. Intestinal dysfunction is a frequent complaint in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients, and previous reports suggest that dysbiosis, i.e. the overgrowth of abnormal populations of bacteria in the gut, is linked to the pathogenesis of the disease.

We used high-throughput 16S rRNA gene sequencing to investigate the presence of specific alterations in the gut microbiota of ME/CFS patients from Belgium and Norway. 43 ME/CFS patients and 36 healthy controls were included in the study. Bacterial DNA was extracted from stool samples, PCR amplification was performed on 16S rRNA gene regions, and PCR amplicons were sequenced using Roche FLX 454 sequencer.

The composition of the gut microbiota was found to differ between Belgian controls and Norwegian controls: Norwegians showed higher percentages of specific Firmicutes populations (Roseburia, Holdemania) and lower proportions of most Bacteroidetes genera. A highly significant separation could be achieved between Norwegian controls and Norwegian patients: patients presented increased proportions of Lactonifactor and Alistipes, as well as a decrease in several Firmicutes populations. In Belgian subjects the patient/control separation was less pronounced, however some abnormalities observed in Norwegian patients were also found in Belgian patients.

These results show that intestinal microbiota is altered in ME/CFS. High-throughput sequencing is a useful tool to diagnose dysbiosis in patients and could help designing treatments based on gut microbiota modulation (antibiotics, pre and probiotics supplementation).

From Graefe's Archive for Clinical and Experimental Ophthalmology, August 2013.

Characterising eye movement dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome

Stephen P. Badham, Claire V. Hutchinson



People who suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often report that their eye movements are sluggish and that they have difficulties tracking moving objects. However, descriptions of these visual problems are based solely on patients’ self-reports of their subjective visual experiences, and there is a distinct lack of empirical evidence to objectively verify their claims. This paper presents the first experimental research to objectively examine eye movements in those suffering from ME/CFS.


Patients were assessed for ME/CFS symptoms and were compared to age, gender, and education matched controls for their ability to generate saccades and smooth pursuit eye movements.


Patients and controls exhibited similar error rates and saccade latencies (response times) on prosaccade and antisaccade tasks. Patients showed relatively intact ability to accurately fixate the target (prosaccades), but were impaired when required to focus accurately in a specific position opposite the target (antisaccades). Patients were most markedly impaired when required to direct their gaze as closely as possible to a smoothly moving target (smooth pursuit).


It is hypothesised that the effects of ME/CFS can be overcome briefly for completion of saccades, but that continuous pursuit activity (accurately tracking a moving object), even for a short time period, highlights dysfunctional eye movement behaviour in ME/CFS patients. Future smooth pursuit research may elucidate and improve diagnosis of ME/CFS.

The authors have no financial relationship with the body that funded this research. The authors have full control of all primary data, and agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data upon request.

From Psychoneuroendocrinology, 2 August 2013.


Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome: A systematic review and subset meta-analysis

Daniel J.H. Powell(a), Corresponding author contact information, E-mail the corresponding author, Christina Liossi(a), Rona Moss-Morrisa(b), Wolff Schlotza(c)
(a) Faculty of Social and Human Sciences, University of Southampton, Southampton, UK
(b) Department of Psychology, Institute of Psychiatry, KCL, London, UK
© Institute of Psychology, University of Regensburg, Regensburg, Germany


The hypothalamic–pituitary–adrenal (HPA) axis is a psychoneuroendocrine regulator of the stress response and immune system, and dysfunctions have been associated with outcomes in several physical health conditions. Its end product, cortisol, is relevant to fatigue due to its role in energy metabolism.

The systematic review examined the relationship between different markers of unstimulated salivary cortisol activity in everyday life in chronic fatigue syndrome (CFS) and fatigue assessed in other clinical and general populations. Search terms for the review related to salivary cortisol assessments, everyday life contexts, and fatigue.

All eligible studies (n = 19) were reviewed narratively in terms of associations between fatigue and assessed cortisol markers, including the cortisol awakening response (CAR), circadian profile (CP) output, and diurnal cortisol slope (DCS). Subset meta-analyses were conducted of case–control CFS studies examining group differences in three cortisol outcomes: CAR output; CAR increase; and CP output.

Meta-analyses revealed an attenuation of the CAR increase within CFS compared to controls (d = −.34) but no statistically significant differences between groups for other markers. In the narrative review, total cortisol output (CAR or CP) was rarely associated with fatigue in any population; CAR increase and DCS were most relevant.

Outcomes reflecting within-day change in cortisol levels (CAR increase; DCS) may be the most relevant to fatigue experience, and future research in this area should report at least one such marker. Results should be considered with caution due to heterogeneity in one meta-analysis and the small number of studies.

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